Certain techniques of analytical chemistry such as mass spectrometry (MS) require that components of a sample be ionized prior to analysis. Generally, MS encompasses a variety of instrumental methods of qualitative and quantitative analysis that enable ionized species of analytes (i.e., sample molecules of interest) to be resolved according to their mass-to-charge ratios. For this purpose, an MS system converts certain components of a sample into ions, sorts, separates or filters the ions based on their mass-to-charge ratios, and processes the resulting ion output (e.g., ion current or flux) as needed to produce a mass spectrum. Typically, a mass spectrum is a series of peaks indicative of the relative abundances of charged components as a function of mass-to-charge ratio.
A typical MS system includes a sample source, an ion source or ionization device, one or more mass analyzers, an ion detector, a signal processor, a readout/display means, and an electronic controller such as a computer. The MS system also includes a vacuum system to enclose the mass analyzer(s) in a controlled, evacuated environment. In atmospheric-pressure ionization (API) techniques, the sample material provided to the ion source is ionized at or near atmospheric pressure in an ionization chamber that is separated from the evacuated regions of the mass analyzer. Ions produced in the atmospheric-pressure ionization chamber are transported into the evacuated environment of the mass spectrometer via a sampling orifice. API techniques are particularly useful when it is desired to couple mass spectrometry with an analytical separation technique such as liquid chromatography (LC). For instance, the eluant from an LC column may serve as the sample source leading into the ionization chamber. Typically, the effluent consists of a liquid-phase matrix of analytes and mobile-phase material (e.g., solvents, additives, buffers).
Examples of API techniques include electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), atmospheric-pressure photo-ionization (APPI), atmospheric-pressure laser ionization (APLI), and atmospheric-pressure matrix-assisted laser desorption/ionization (AP-MALDI). API techniques such as these are known and therefore need not be described in detail.
In the case of ESI, a liquid sample is introduced into the ionization chamber through an electrospray needle. A voltage potential is applied between the needle and a secondary electrode (or counter-electrode) in the ionization chamber to establish an electric field within the ionization chamber. The electric field induces charge accumulation at the surface of the liquid at or near the tip of the needle, and the liquid sample is discharged from the needle in the form of highly charged droplets (electrospray). The breaking of the stream of liquid into a mass of fine droplets, or aerosol, may be assisted by a nebulizing technique that may involve pneumatic, ultrasonic, thermal or electrostatic means. For example, pneumatic nebulization may be implemented by providing a tube coaxial to the electrospray needle and discharging an inert gas such as nitrogen coaxially with the sample liquid. An electric field directs the charged droplets from the tip of the electrospray needle toward the sampling orifice that leads from the ionization chamber to the mass spectrometer. The droplets undergo a process of desolvation or ion evaporation as they travel through the ionization chamber. As solvent contained in the droplets evaporates, the droplets become smaller. In addition, the droplets may rupture and divide into even smaller droplets as a result of repelling coulombic forces approaching the cohesion forces of the droplets. Eventually, charged analyte molecules (analyte ions) desorb from the surfaces of the droplets. More recently, low-flow electrospray and nano-electrospray techniques have been developed. Low-flow electrospray and nano-electrospray techniques entail flowing the liquid sample through a small-bore needle (or sample emitter) at a micro-scale or nano-scale flow rate. These techniques can be advantageous in that a lesser amount of sample is required, assisted nebulization is not required to form fine droplets, ions are liberated from the sample primarily through the mechanism of ion evaporation, and a higher ion signal-to-noise ratio (S/N) may be achieved.
In any API technique, ideally only the analyte ions enter the mass spectrometer, and not the other components of the sample spray such as neutral solvated droplets, or air or oxygen. To this end, a stream of an inert (and typically heated) drying gas such as nitrogen is introduced into the ionization chamber to assist in the evaporation of solvent and/or sweep the solvent away from the sampling orifice leading into the mass spectrometer, as well as to assist in the evaporation and desolvation of ions from the sample spray. Conventionally, the drying gas is introduced through one or two openings in counterflow relation to the spray as the spray approaches the sampling orifice. Alternatively, the drying gas is introduced as a curtain in front of the sampling orifice. In conventional API apparatus, the velocity and path of the drying gas entering the ionization chamber is not optimized for collecting analyte ions and producing a good ion signal from the sample material. The high-velocity drying gas creates unwanted gas turbulence in the ionization chamber that disrupts the sample spray, particularly in implementations where the sample spray is a low-flow electrospray or nano-electrospray. Additionally, the geometry of the ionization chamber and the components contained therein such as the secondary electrode—as well as the velocity, degree of turbulence, and path of the drying gas—have been found to create a low-pressure gas stagnation zone in front of the secondary electrode. Little or no gas flows in this stagnation zone. Also, the stagnation zone fluctuates into and out from the sample spray, thereby significantly perturbing the sample spray and contributing to its instability. Moreover, the drying gas is directed in a manner that fails to heat the ionization chamber uniformly, and may leave the majority of the ionization chamber unheated. As a result, in some designs it may be difficult to achieve a stable, smooth liquid sample spray from the sample emitter, and to achieve a uniformly heated environment conducive to aiding in the production of ions, and high-mass ions in particular. In addition, the unstable sample spray allows some of the droplets to enter the capillary and consequently the mass analyzer of the mass spectrometer. The admission of droplets into the mass spectrometer is highly undesirable, as these droplets cause contamination to the inlet parts of the mass spectrometer which in turn requires more frequent cleaning of these parts and the attendant downtime involved. Moreover, these droplets impair the ion signal from which analytical data is derived and lower the sensitivity of the mass spectrometer.
In view of the foregoing, there is an ongoing need for API apparatus that address the problems mentioned above.